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The first two cell-fate decisions of preimplantation mouse embryo development are not functionally independent
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SYSNO ASEP 0451070 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The first two cell-fate decisions of preimplantation mouse embryo development are not functionally independent Author(s) Mihajlović, A. I. (CZ)
Thamodaran, V. (CZ)
Bruce, Alexander (BC-A) RIDNumber of authors 3 Source Title Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 5, article no. 15034 (2015)Number of pages 16 s. Language eng - English Country GB - United Kingdom Keywords primitive endoderm formation Subject RIV EB - Genetics ; Molecular Biology Institutional support BC-A - RVO:60077344 UT WOS 000362642100002 EID SCOPUS 84944187093 DOI 10.1038/srep15034 Annotation During mouse preimplantation embryo development, three distinct cell lineages are formed, represented by the differentiating trophectoderm (TE), primitive endoderm (PrE) and the pluripotent epiblast (EPI). Classically, lineage derivation has been presented as a two-step process whereby outer TE cells are first segregated from inner-cell mass (ICM), followed by ICM refinement into either the PrE or EPI. As ICM founders can be produced following the fourth or fifth cleavage divisions, their potential to equally contribute to EPI and PrE is contested. Thus, modelling the early sequestration of ICM founders from TE-differentiation after the fourth cleavage division, we examined ICM lineage contribution of varying sized cell clones unable to initiate TE-differentiation. Such TE-inhibited ICM cells do not equally contribute to EPI and PrE and are significantly biased to form EPI. This bias is not caused by enhanced expression of the EPI marker Nanog, nor correlated with reduced apical polarity but associated with reduced expression of PrE-related gene transcripts (Dab2 and Lrp2) and down-regulation of plasma membrane associated Fgfr2. Our results favour a unifying model were the three cell lineages are guided in an integrated, yet flexible, fate decision centred on relative exposure of founder cells to TE-differentiative cues. Workplace Biology Centre (since 2006) Contact Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Year of Publishing 2016 Electronic address http://www.nature.com/articles/srep15034
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